This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Metabolites play a key role in regulating biological function by activating or inhibiting both gene expression and enzyme activity. Therefore, the quantification of metabolites in a system allows for the comparative analysis of biological samples (systems biology). The development of technologies that allow for the comprehensive quantitative measurement of metabolites will be a crucial first step in restoring metabolic balance and mitigating symptoms of certain diseases. In order to quantify and compare metabolites, they must be selectively labeled with isotopic markers such that molecules are readily recognized by spectroscopy techniques. Novel chemical reagents are herein proposed that will target the most prevalent metabolite functional groups and allow for the quantification of a large number of the key metabolites of biological systems.